N⁶-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N⁶-propyl-5,6,7,8-tetrahydronaphthalene-2,3,6-triamine | 1434078-96-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N⁶-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N⁶-propyl-5,6,7,8-tetrahydronaphthalene-2,3,6-triamine
• CAS: 1434078-96-2
• 化学式: C₂₆H₃₉N₅O
• 分子量: 437.629
• InChiKey: LTLBTEWPTBLFOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  70.99
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  二硫化碳 、 N⁶-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N⁶-propyl-5,6,7,8-tetrahydronaphthalene-2,3,6-triamine 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以84%的产率得到6-[2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl-propylamino]-1,3,5,6,7,8-hexahydrobenzo[f]benzimidazole-2-thione
  参考文献：
  名称：

  Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors

  摘要：

  The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D-3 versus D-2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K-i) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed in the GTP gamma S binding assay. In the imidazole series, compound 10a exhibited the highest D-3 affinity whereas the indole derivative 13 exhibited similar high D-3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D-3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.059
• 作为产物：
  描述：

  在 盐酸 、 palladium 10% on activated carbon 、 水 、 氢气 、 硝酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -50.0~20.0 ℃ 、482.64 kPa 条件下， 反应 66.0h， 生成 N⁶-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N⁶-propyl-5,6,7,8-tetrahydronaphthalene-2,3,6-triamine
  参考文献：
  名称：

  Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors

  摘要：

  The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D-3 versus D-2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K-i) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed in the GTP gamma S binding assay. In the imidazole series, compound 10a exhibited the highest D-3 affinity whereas the indole derivative 13 exhibited similar high D-3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D-3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.059